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Biomedical subjects

M Juan

Publications and source records attributed to M Juan.

At least 19 recordsLinked to original sources
PubMed2006

[Prenatal cerebrovascular accidents: their incidence, pathogenesis and risk factors].

INTRODUCTION: Prenatal stroke appears to have different risk factors, clinical characteristics, and outcomes than other perinatal or childhood stroke syndromes. DEVELOPMENT: Fetal stroke is defined as any cerebrovacular episode that occurs between 14 weeks of gestation and the onset of labor resulting in delivery, has been associated with postnatal epilepsy, mental retardation, and cerebral palsy. The entity is caused by antenatal ischemic, thrombotic, or hemorrhagic injury. A better understanding of those risk factors predisposing a fetus to cerebral infarction may provide a basis for future intervention for prevention and therapy. We will review the incidence, definition, pathogenesis, and risk factor of this entity that is more and more recognized. CONCLUSION: The analysis of this data will allow us to compare different method of evaluation and to draw conclusion of possible screening method and early detection.

Fetal Diseases↗
PubMed2006

One-tube-PCR technique for CCL2, CCL3, CCL4 and CCL5 applied to fine needle aspiration biopsies shows different profiles in autoimmune and non-autoimmune thyroid disorders.

Autoimmune thyroid diseases are characterized by lymphocytic infiltration of the thyroid gland. Chemokines are crucial in the recruitment of lymphocytes and might play an important role in the pathogenesis of autoimmune thyroid disease. The aim of this study was to test the feasibility of analysing by one-tube reverse-transcriptase polymerase chain reaction (RT-PCR) technique CC chemokine profiles in samples obtained by fine needle aspiration biopsy (FNAB). In 27 out of 35 (77%) samples, the material was sufficient for analysis and in 16 (59%) chemokines were detected, thus demonstrating the potential of this technique. Moreover, even in this small group, a statistically significant increase of CCL3 and CCL4 was found in samples from patients with autoimmune thyroid disease as compared to those with multinodular goiter. Chemokine profile measured by improved multiamplification techniques in FNAB thyroid samples may become a useful complementary tool for the management of thyroid autoimmune disease as it constitutes a source of data for research of their pathogenesis.

Adult↗
PubMed2001

[Reduction of hematogenous infection in HIV positive patients following highly active antiretroviral therapy].

BACKGROUND: Bloodstream infections have probably decreased in HIV patients since highly active antiretroviral therapy (HAART) usage. PATIENTS AND METHOD: Hematogenous infections, including mycobacteria and fungi in HIV patients, stratified into two periods (I: 1995-1996 and II: 1997-1998) were included to evaluate changes attributable to HAART. RESULTS: 226 episodes were attended (incidence: 38.8 in period I and 15.3 in period II; p < 0.01). A significant decrease was observed in immunosuppression related microorganisms. HAART usage increased from 6.4% in period I to 31.2% in period II. Immunological parameters of HIV patients significantly improved in period II. CONCLUSIONS: Hematogenous infections have significantly decreased in HIV patients since the use of HAART.

AIDS-Related Opportunistic Infections↗
PubMed2001

Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers.

Autoimmune thyroid disease--Hashimoto thyroiditis and Graves' disease--patients produce high levels of thyroid autoantibodies and contain lymphoid tissue that resembles secondary lymphoid follicles (LFs). We compared the specificity, structure, and function of tonsil and lymph node LFs with those of the intrathyroidal LFs to assess the latter's capability to contribute to autoimmune response. Thyroglobulin and thyroperoxidase binding to LFs indicated that most intrathyroidal LFs were committed to response to thyroid self-antigens and were associated to higher levels of antibodies to thyroglobulin, thyroperoxidase, and thyroid-stimulating hormone receptor. Intrathyroidal LFs were microanatomically very similar to canonical LFs, ie, they had well-developed germinal centers with mantle, light, and dark zones and each of these zones contained B and T lymphocytes, follicular dendritic and interdigitating dendritic cells with typical phenotypes. Careful assessment of proliferation (Ki67) and apoptosis (terminal dUTP nick-end labeling) indicators and of the occurrence of secondary immunoglobulin gene rearrangements (RAG1 and RAG2) confirmed the parallelism. Unexpected high levels of RAG expression suggested that receptor revision occurs in intrathyroidal LFs and may contribute to generate high-affinity thyroid autoantibodies. Well-formed high endothelial venules and a congruent pattern of adhesion molecules and chemokine expression in intrathyroidal LFs were also detected. These data suggest that ectopic intrathyroidal LFs contain all of the elements needed to drive the autoimmune response and also that their microenvironment may favor the expansion and perpetuation of autoimmune response.

Adult↗
PubMed2001

Cutaneous angiolymphoid hyperplasia with high endothelial venules is characterized by endothelial expression of cutaneous lymphocyte antigen.

Two cases in which the presence of cutaneous lesions with a characteristic admixture of lymphoid hyperplasia and vascular proliferation lead to the diagnosis of so-called acral pseudolymphomatous angiokeratoma (APA) of children are reported. Owing to the prominence of its blood vessels, so striking as to be reminiscent of high endothelial venules (HEVs), APA was initially interpreted as a vascular lesion rather than a pseudolymphoma. This resemblance is further compounded by our finding that cutaneous lymphocyte antigen (CLA), an HEV marker, is also expressed in APA epithelioid blood vessels. Consequently, we believe that "cutaneous angiolymphoid hyperplasia with high endothelial venules" (ALH-HEV), which alludes to the dual nature of proliferating elements and the HEV-like phenotype of the vascular component, would be a better denomination for this entity. Additionally, we speculate that ALH-HEV lymphoid hyperplasia self-perpetuates through the transformation of dermal capillaries into HEVs, which would bind non-skin homing lymphocytes expressing L-selectin and promote their local recruitment and recirculation.

Angiokeratoma↗
PubMed2001

Liver transplantation in patients with portal vein thrombosis.

The aim of this study is to analyze the incidence, risk factors, management, and follow-up of patients with portal vein thrombosis (PVT) undergoing primary orthotopic liver transplantation (OLT). Four hundred fifteen OLTs were performed in 391 patients. In 62 patients, partial (group 1; n = 48) or complete (group 2; n = 14) PVT was found at the time of surgery. Portal flow was reestablished by venous thrombectomy. In this study, we compare 62 primary OLTs performed in patients with PVT at the time of OLT with a group of 329 primary OLTs performed in patients without PVT (group 3) and analyze the incidence of PVT, use of diagnostic methods, surgical management, and outcome. We found no significant differences among the 3 groups for length of surgery, cold and warm ischemic times, and postoperative stay in the intensive care unit. With the piggyback technique, groups 1 and 2 had greater blood losses and required more blood transfusions than group 3. The early reoperation rate was greater in group 2. The incidence of rethrombosis was 4.8% (group 1, 2%; group 2, 14.3%). Reexploration and thrombectomy (2 patients) and retransplantation (1 patient) had a 100% mortality rate. In particular, the mortality rate of patients with complete PVT with extension into the splanchnic veins is high (33%). Three-month and 4-year patient survival rates were statistically similar in the 3 groups. The presence of PVT at the time of OLT is not a contraindication for OLT. However, if PVT extends into the splanchnic veins, the outcome is guarded.

Adult↗
PubMed2001

Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone.

Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGRalpha and hGRbeta. We analyzed the expression and regulation of both hGR isoforms in human respiratory epithelial cells (BEAS-2B, A549, and primary nasal epithelial cells). In BEAS-2B cells, the expression of hGRalpha messenger RNA (mRNA) was much higher than that of hGRbeta mRNA. Dexamethasone (DEX) (10(-6) M) downregulated hGRalpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGRbeta mRNA only at 6 h (55 +/- 7% of control; P < 0.01). Downregulation of hGRalpha and hGRbeta mRNAs occurred even in the presence of cycloheximide. Actinomycin-D studies revealed that DEX enhanced the stabilization of hGRalpha and hGRbeta messages. hGRalpha but not hGRbeta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGRalpha protein in BEAS-2B, A549, and nasal epithelial cells (16 +/- 4, 14 +/- 4, and 28 +/- 7% of control, respectively; P < 0.01). These results suggest that in respiratory epithelial cells: (1) hGRalpha is much more expressed than hGRbeta at both the mRNA and protein levels; (2) hGRalpha is downregulated by corticosteroids both in cell lines (BEAS-2B, A549) and in nasal primary cells; and (3) transcriptional, post-transcriptional, and post-translational mechanisms appear to be involved in the regulation of hGR expression by corticosteroids.

Animals↗
PubMed1999

Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways.

T-lymphocyte migration into tissues requires focal degradation of the basement membrane. In this study, we show that transient adherence to fibronectin induces the production of activated forms of matrix metalloproteinase-2 (MMP-2) and MMP-9, as well as downregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) by T-cell lines. MMP-2 activation was likely achieved by inducing a coordinated expression of membrane-type matrix metalloproteinase-1 (MMP-14), a major activator of MMP-2. Blocking monoclonal antibodies against alpha4, alpha5, and alphav integrins strongly reduced MMP-2 and MMP-9 production induced by fibronectin. Disrupting actin cytoskeleton organization by cytochalasin D strongly enhanced fibronectin-induced MMP-2 and MMP-9 expression. Inhibiting Src tyrosine kinases with herbimycin A reduced MMP-2 and MMP-9 production with no effect on cell attachment. By contrast, G-protein inhibition by pertussis toxin, or transfection with a dominant negative mutant of Ha-Ras strongly increased fibronectin-induced MMP-2 and MMP-9. Inhibition of PI3 kinase, MAPkinase (MEK1), or p38 MAPkinase by wortmannin, PD 98059, or SB 202190, respectively, strongly promoted fibronectin-induced MMP2 and MMP-9. Cells at high density lost their ability to synthesize MMP-2 and MMP-9 in response to fibronectin and MMP expression was restored by transfection with a dominant-negative mutant of Ha-Ras or by treatment with wortmannin, PD 98059, or SB 202190. Our findings suggest that adhesion to fibronectin transduces both stimulatory (through Src-type tyrosin kinases) and inhibitory signals (through Ras/MAPKinase signaling pathways) for MMP-2 and MMP-9 expression by T lymphocytes and that their relative predominance is regulated by additional stimuli related to cell adhesion, motility, and growth.

Androstadienes↗
PubMed1999

Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function.

Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17beta-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in beta1, alpha5 and alpha6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation, the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens can promote neovascularization and vessel repair.

Journal Article↗
PubMed1999

Efficacy and safety of cardiomyotomy in patients with achalasia after failure of pneumatic dilatation.

In patients with achalasia, it has been suggested that pneumatic dilatation could make cardiomyotomy more difficult to perform, diminishing its efficacy and safety. Our aim was to evaluate the efficacy and safety of elective cardiomyotomy after failure of pneumatic dilatation in achalasia. During 14 years, 32 of 276 consecutive patients with achalasia have been operated on because of failure of dilatation therapy. Twenty patients have been followed-up for at least one year after surgery. After failure of dilatation, Heller's cardiomyotomy and 180 degrees anterior fundoplication were performed. Clinical status was evaluated before and after surgery. Lower esophageal sphincter pressure and esophageal body basal pressure were measured by manometry, esophageal diameter by barium meal, and gastroesophageal reflux by endoscopy and 24-hr esophageal pH monitoring. No technical difficulties were found during operation. Postoperative morbidity was infrequent and mortality was absent. Cardiomyotomy improved clinical status in 19 of 20 patients. The results of surgery were considered excellent or good in 16 patients (80%; CI: 56-94%). The pressure of the lower esophageal sphincter was significantly reduced, falling in most patients to under 10 mm Hg. Gastroesophageal reflux appeared after surgery in eight patients, four of them with endoscopic esophagitis, but it was controlled in all patients with medical therapy. In conclusion, cardiomyotomy is a safe and effective therapy in achalasia after failed pneumatic dilatation.

Adult↗
PubMed1999

Regulation of ICAM-3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone.

BACKGROUND: ICAM-3 has been recently identified as the third leukocyte-function associated-1 (LFA-1) ligand. ICAM-3 is expressed in eosinophils, but its regulation has not been studied. The objective of this study was to investigate the differential expression of ICAM-3 and other adhesion molecules (AM) on the surface of eosinophils. We also evaluated the effects of dexamethasone on AM expression. METHODS: Normodense eosinophils were isolated from peripheral blood and incubated with calcium ionophore A23187 (calcimycin) with and without dexamethasone. Expression of AM was assessed by flow cytometry and expressed as fluorescence mean intensity (FMI). RESULTS: Peripheral blood eosinophils constitutively expressed low levels of ICAM-1 and ICAM-2 (<10 FMI), moderate levels (10-50 FMI) of CD29 and L-selectin, and high levels (>50 FMI) of ICAM-3, LFA-1, and Mac-1. Calcium ionophore (1 microM) significantly increased Mac-1 and ICAM-1 expression at 6 and 24 h. L-selectin expression decreased at 6 and 24 h, but ICAM-2, ICAM-3, LFA-1, and CD29 expression did not show any significant change after calcium ionophore stimulation. Dexamethasone decreased ICAM-3 and increased L-selectin basal expression, and it caused a dose-related inhibition of calcium ionophore-induced ICAM-1 expression. CONCLUSIONS: These findings suggest that some AM, such as ICAM-1, Mac-1, and L-selectin, may be involved in adhesion during eosinophil activation and that glucocorticoids may prevent airway inflammation by regulating the expression of AM in eosinophils. The role of ICAM-3, a leukocyte AM highly expressed in resting eosinophils, remains to be clarified.

Antigens, CD↗
PubMed1999

Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with </=250/microL CD4 T cells and undetectable plasma virus load.

The immunologic efficacy of low-dose recombinant interleukin-2 (rIL-2) administered subcutaneously (sc) once a day in combination with highly active antiretroviral therapy (HAART) was assessed in a pilot study in patients with advanced human immunodeficiency virus (HIV) disease. Twenty-five persons with </=250 CD4 cells/microL and plasma HIV-1 RNA levels </=500 copies/mL for >24 weeks were randomly assigned to receive sc rIL-2 (3 x 10(6) IU once a day) with their previous antiretroviral regimen (n=13) or to continue with the same treatment (n=12). The level of CD4 T cells was significantly higher in the IL-2 group at week 24 (105+/-65/microL; P<.05) but not in the control group (30+/-78/microL). Memory T cells initially contributed to the CD4 T cell increase at week 4 (P<.05). Naive T cell increases (99+/-58/microL) in the IL-2 group became statistically significant at week 24 compared with the control group (28+/-27/microL; P<.05). Subcutaneous rIL-2 once a day in combination with HAART was well tolerated and improved immunologic surface markers in patients with advanced HIV infection.

Adult↗
PubMed1999

Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics.

Exogenous prostaglandin E2 (PGE2) given by inhalation almost completely abrogates aspirin-induced asthma and the accompanying increase in cysteinyl-leukotrienes production. Cyclooxygenase (COX) may be present in cells in both constitutive (COX-1) and inducible (COX-2) forms. To increase the production of the potentially protective endogenous PGE2, COX-2 should be upregulated. We hypothesize that an abnormal regulation of COX-2 will predispose patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR). We therefore examined the expression of COX-2 messenger RNA (mRNA) in healthy nasal mucosa (n = 11) and in nasal polyps from both patients with AIAR (n = 8) and those with aspirin-tolerant asthma/rhinitis (ATAR) (n = 20). After total mRNA extraction, COX-1 and COX-2 mRNA expression were measured using a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid primers of COX-1. glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2. GAPDH were used to create PCR products that were cloned and used as internal standard controls in the competitive PCR reaction. Results are presented as mean +/- standard error of 10(6) molecules of mRNA/micrograms of total RNA. No differences in COX-1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR. However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 +/- 0. 52, sevenfold, p < 0.0001) and nasal mucosa (2.10 +/- 0.54, sixfold, p < 0.01). These findings suggest that an inadequate COX-2 regulation may be involved in AIAR.

Adult↗
PubMed1998

Transcription of a broad range of self-antigens in human thymus suggests a role for central mechanisms in tolerance toward peripheral antigens.

The role of the thymus in the induction of tolerance to peripheral antigens is not yet well defined. One impending question involves how the thymus can acquire the diversity of peripheral nonthymic self-Ags for the process of negative selection. To investigate whether peripheral Ags are synthesized in the thymus itself, we have determined the expression of a panel of circulating and cell-bound peripheral Ags, some of which are targets of autoimmune diseases, at the mRNA level in total thymic tissue and in its main cellular fractions. Normalized and calibrated RT-PCR experiments demonstrated the presence of transcripts of nonthymic self-Ags in human thymi from 8 days to 13-yr-old donors. Out of 12 glands, albumin transcripts were found in 12; insulin, glucagon, thyroid peroxidase, and glutamic acid decarboxylase (GAD)-67 in six, thyroglobulin in five, myelin basic protein and retinal S Ag in three, and GAD-65 in one. The levels of peripheral Ag transcripts detected were age-related but also showed marked interindividual differences. Cytokeratin-positive stromal epithelial cells, which are a likely cellular source for these, contained up to 200 transcript copies of the most expressed peripheral Ags per cell. These results implicate the human thymus in the expression of wide representation of peripheral self-Ags and support the view that the thymus is involved in the establishment of tolerance to peripheral Ags. The existence of such central mechanism of tolerance is crucial for the understanding of organ-specific autoimmune diseases.

Adolescent↗
PubMed1998

Impact on the immune system of undetectable plasma HIV-1 RNA for more than 2 years.

OBJECTIVE: To investigate the impact of prolonged HIV suppression on the immune system by analysing the expression of several lymphocyte surface markers in a group of HIV-1-infected patients who maintained undetectable HIV-1 RNA levels for more than 24 months. PATIENTS AND METHODS: The study included a highly selected group of nine HIV-1-infected asymptomatic subjects and seven HIV-1-seronegative controls. The inclusion criteria of HIV-1-infected patients was to have plasma HIV-1 RNA levels below 20 (1.3 log10) copies/ml for at least 24 months while under antiretroviral treatment with nucleoside analogues. The patient population was retrospectively taken from a cohort of 1418 treated subjects. Mean initial absolute CD4+ T-cell count and percentage were 468+/-234 x 10(6)/l (range, 202-935 x 10(6)/l) and 25+/-6% (range, 16-33%), respectively. Plasma HIV-1 RNA quantification was determined using a standard and ultrasensitive reverse transcriptase polymerase chain reaction assay. Median HIV-1 RNA plasma level before antiretroviral treatment was 3.14 log10 copies/ml (range, 1.74-3.73 log10 copies/ml). Two or three-colour immunophenotyping was performed on whole blood and frozen peripheral blood mononuclear cells by flow cytometry. RESULTS: A significant increase was noted in CD4+ lymphocyte counts at the end of the study in HIV-1-positive patients. In addition, the CD4: CD8 ratio rose significantly with respect to baseline, although it remained lower than in the controls. CD45RA+ and CD45RO+ population percentages did not differ between groups. A significant rise in CD45RA+ T cells was observed. Analysis of T-cell activation measuring the expression of human leukocyte antigen-DR and CD25 did not differ between groups. The proportion of CD8+ lymphocytes that were CD28+ was similar in both groups at the end of the follow-up. T-cell receptor Vbeta subfamily analysis showed that an expansion of the T-cell receptor repertoire might occur in these patients. CONCLUSION: Patients who maintain undetectable viral load for prolonged periods of time with antiretroviral therapy may achieve a partial immune restoration of the immune system. Our results suggest that treatment of patients at early stages of HIV infection is warranted.

CD4 Lymphocyte Count↗